Qin Yingying, Choi Youngsok, Zhao Han, Simpson Joe Leigh, Chen Zi-Jiang, Rajkovic Aleksandar
Center for Reproductive Medicine, Shandong Provincial Hospital of Shandong University, Jinan, China.
Am J Hum Genet. 2007 Sep;81(3):576-81. doi: 10.1086/519496. Epub 2007 Jul 10.
NOBOX (newborn ovary homeobox gene) is an oocyte-specific homeobox gene that plays a critical role in early folliculogenesis and represents a candidate gene for nonsyndromic ovarian failure. We investigated whether mutations in the NOBOX gene cause premature ovarian failure (POF). We sequenced the NOBOX gene in 96 white women with POF and discovered seven known single-nucleotide polymorphisms and four novel variations, two of which, p.Arg355His and p.Arg360Gln, cause missense mutations in the homeobox domain. Electrophoretic mobility shift assay (EMSA) confirmed that the missense mutation, p.Arg355His, disrupted NOBOX homeodomain binding to NOBOX DNA-binding element (NBE) and had a dominant negative effect on the binding of wild-type NOBOX to DNA. Our findings demonstrate that NOBOX mutations can cause POF.
NOBOX（新生儿卵巢同源框基因）是一种卵母细胞特异性同源框基因，在早期卵泡发生过程中起关键作用，是散发性卵巢功能不全的一个候选基因。我们研究了NOBOX基因突变是否会导致卵巢早衰（POF）。我们对96名患有POF的白人女性的NOBOX基因进行了测序，发现了7个已知的单核苷酸多态性和4个新的变异，其中两个，即p.Arg355His和p.Arg360Gln，在同源框结构域中引起错义突变。电泳迁移率变动分析（EMSA）证实，错义突变p.Arg355His破坏了NOBOX同源结构域与NOBOX DNA结合元件（NBE）的结合，并对野生型NOBOX与DNA的结合产生显性负效应。我们的研究结果表明，NOBOX突变可导致POF。
